EllRPEAN

,OURNl,

OF

CARDIO-THORACIC
SURGERY

European Journal of Cardio-thoracic

Development

of a non-pulsatile
Yukihiko

Surgery 11 Suppl. (1997) S32-S38

permanent

rotary blood pump

Nose *, Koji Kawahito

Baylor College of Medicine, Department of Surgery, One Baylor Plaza, Houston TX 77030, USA

Abstract
For many years, a common belief was that non-pulsatile
perfusion produced physiological
and circulatory abnormalities.
Since
1977 our group has reported, if a 20% higher blood flow was used more than required for a pulsatile blood pump, there would
be no circulatory or physiological
abnormalities.
These experimental
findings confirmed that there was no difference in clinical
outcome when using a pulsatile or non-pulsatile
blood pump. Furthermore,
the non-pulsatile
rotary blood pump has demonstrated efficient and reliable performance
in various clinical situations. The non-pulsatile
blood pump is a simple and reliable
design, that can be easily manufactured,
and has the following desirable features. There is no need to incorporate
heart valves,
a large orifice inflow conduit, or a compliance volume-shifting
chamber. Since an electrical motor operates continuously,
the
on-and-off
motion required for a pulsatile pump is not necessary; therefore, it becomes a more efficient and durable system.
Further, the control algorism is simpler and more reliable than a pulsatile pump. Considering
these factors, the non-pulsatile
blood pump can be selected for a permanently
implantable assist device. To develop an implantable non-pulsatile
cardiac device,
it is necessary to incorporate
seven features in the system such as: small size, atraumatic
features, anti-thrombogenic
features,
anti-infection
features, durable and simple design, and low energy requirement with easy controllability.
0 1997 Elsevier Science
B.V.

1. Justification

of non-pulsatile

perfusion

The clinical results show that the centrifugal

pumps
which provide non-pulsatile
circulation
as ventricular
assist devices for post-cardiotomy
cardiogenic
shock is
the same as that of the pneumatic pulsatile flow devices
even though the pumps were developed for cardiopulmonary bypass [l-4]. In experimental
data, Griffith et
al. reported
that pulseless flow and relief from the
demands of external work provided by left ventricular
bypass with a centrifugal
pump system permitted adequate myocardial
perfusion
at normal coronary
flow
rates without
myocardial
ischemia
or acidosis
[5].
Moreover, Kanamori
et al. noted that the non-pulsatile
left ventricular assist was more effective on reducing left
ventricular
work and myocardial
oxygen consumption
*Corresponding author. Tel.: + 1 713 7983930; fax: + 1 713
7983985.

This paper is based on a presentation given by Yukihiko Nose at

the 5th International
Symposium
Bad Oyeuhausen
Mechanical
Support 95, Bad Oyeuhausen,
Germany on October 1995.
lOlO-7940/97/%17.00
C 1997 Elsevier
PIISlOlO-7940(97)01188-3

Science B.V. All rights

reserved.

than pulsatile ventricular

assist if a higher left heart
bypass flow was maintained
(more than 75% bypass
rate) [6]. Therefore,
it is clear that the effectiveness of
non-pulsatile
circulatory
support is at least the same as
that of pulsatile circulatory
support in terms of ventricular assistance or saving of the diseased heart.
The main concern is whether non-pulsatile
circulation will maintain
the normal physiology
of all body
organs, or whether non-pulsatile
circulation
will apply
to a long term life support system. Since 1977, these
authors have been involved in the investigation
of the
physiological
responses to non-pulsatile
total body perfusion [7].
Traditionally,
it was considered
that non-pulsatile
perfusion
was not good for the physiology.
During
1976, Johnston,
Bernstein
and colleagues
conducted
studies on the pulseless LVAD for 2 weeks in calves [8].
They demonstrated
that various physiological
abnormalities
occurred
in the pulseless
animals.
Higher
venous pressure, higher cardiac output, and varied peripheral resistance were among the abnormalities.

Y. Nose, K. Kawahito /European

Journal of Cardio-thoracic Surgery 1 I Suppl. (1997) S32-S38

We have been implanting cardiac prostheses in calves

for many years while maintaining normal circulatory
parameters in a pulsatile mode of perfusion. However,
during the initial 2 weeks after implantation of a pulsatile cardiac prostheses, we have seen non-physiological circulatory parameters in this group of animals [9].
At that time many research groups had shown high
peripheral resistance (initially within a few days), high
venous pressure, and increased circulating blood volume during this period. After pumping for more than 2
weeks, this abnormal physiology often has a tendency
to disappear. The results that Johnston et al. observed
with a non-pulsatile mode of perfusion in 2 weeks were
identical to what we have seen with the pulsatile mode
of total body perfusion.
These authors studied pulseless total body perfusion
for both the right and left circulation utilizing centrifugal pumps. The total bypass was made for the right and
left heart, and blood flow was maintained as high as
possible. During this bypass procedure, the natural
heart was sustained in a ventricular fibrillation state
[lo]. Five animals were kept for l- and 3-month periods
[ 11,121. Implanted pumps were exchanged every 2
weeks to avoid thromboembolic complications. Comparative studies were conducted in hemodynamics and
other physiological parameters with the pulsatile TAH
animals [13,14].
As was predicted in the non-pulsatile group, it was
initially very difficult to maintain sufficient blood flow
together with high peripheral resistance for 2 days [14].
Despite the initial difficulty in maintaining the higher
flow, all the long-term survival animals had maintained
a blood flow of 110 ml/kg or higher for at least the
initial 6 weeks. The blood flow used for the pulsatile
TAH was usually below 100 ml/kg. Under these conditions, the near normal physiology of the calves with
both non- and pulsatile artificial hearts were observed.
We recognized that it is extremely important to keep a
20% higher blood flow if the non-pulsatile mode of
perfusion is applied [15].
The high left atria1 pressure, which was very difficult
to reduce in the non-pulsatile group of animals, almost
reached the same level as that of the pulsatile animals
after 2 weeks of perfusion. The same range of circulatory blood volume was maintained in both the pulsatile
and non-pulsatile modes of perfusion. The right atria1
pressure in both groups had a tendency to increase
during the initial 2 weeks; however, after 2 weeks it had
a tendency to decrease in the same fashion.
In both groups, the catecholamine level was initially
increased. Particularly in the non-pulsatile mode of
perfusion, the level measured during the initial few days
of perfusion was approximately two times higher. However, after 2 weeks of perfusion, the level became the
same in both groups [14].

s33

Higher SGOT levels in the pulsatile and non-pulsatile

modes of perfusion in the first week were seen; however, again after 2 weeks of perfusion, the SGOT levels
in both groups became the same as the control levels.
Colloid osmotic pressure, serum osmotic pressure, and
red cell mass volume did not show any differences in
these two groups of animals during these initial 2 weeks

V61.
Treadmill exercise tests demonstrated that both nonand pulsatile groups showed moderate to good tolerance at 1.5 mph tests without hemodynamic
or
metabolic deterioration [17- 191. The increased 0, demand during exercise was met by augmented 0, extraction for non-pulsatile
bi-ventricular
bypass while
increased cardiac output and 0, extraction for pulsatile
TAH recipients. The non-pulsatile group has a higher
norepinephrine response to exercise than the pulsatile
TAH group. Although patients can tolerate moderate
exercise with the constant flow of non-pulsatile circulation, a regulation system which can increase pump flow
during exercise is necessary for a higher quality of life.
Thus, our experiences demonstrate that if a 20%
higher blood flow was used more than that required for
a pulsatile blood pump, there would be no circulatory
or physiological abnormalities.
These experimental
findings confirm that there is no difference in the clinical outcome if we use a pulsatile or a non-pulsatile
blood pump as a permanent blood pump. Based on this
information, a non-pulsatile blood pump can be chosen
as a long-term implantable blood pump.

2. Desirable features of the non-pulsatile

blood pump

Non-pulsatile rotary blood pump demonstrates an

efficient and reliable performance in various clinical
situations. The non-pulsatile rotary blood pump is a
simple and reliable design, that is easily manufactured,
and has the following desirable features:
1. There is no need to incorporate heart valves, the
most thrombogenic
and blood trauma inducing
components of a pump design.
2. A continuous flow pump does not require a large
orifice inflow conduit and is proven to be easier to
implant in patients, with minimal damage to the
myocardium.
Table 1
Seven features

to develop

Small size
Atraumatic
features
Anti-thrombogenic
features
Anti-infection
features
Durable and simpler design
Lower energy requirement
Easy controllability

a totally

implantable

non-pulsatile

pump

s34

Y. Nose, K. Kawahito /European Journal of Cardio-thoracic Surgery I1 Suppl. (1997) S32438

Fig. 1. (Comparative picture of an electro-mechanical pulsatile LVAD (left ventricular assist device) (right) and DeBakey/NAS A axial flow L\ AD
(left). The volume of this axial flow LVAD is only 15 ml.

3. There is no need to incorporate

a compliance volume-shifting device, which is essential for a pulsatile

blood pump. The implantation of additional intrathoracic hardware is eliminated in a continuous flow
pump.
4. In the continuous blood pump, the control algorism
is simpler and more reliable than a pulsatile pump.
5. Due to a rotary blood pumps structure, only one
moving part is necessary for the blood pumping
motion. By using durable components for this moving part, an overall durable system becomes possible.
6. Since an electrical motor operates continuously, the
on-and-off motion required for a pulsatile pump is
unnecessary; therefore, it becomes a more efficient
and durable system.

3. Seven features to develop a permanent implantable

non-pulsatile pump

In order to achieve a permanently implantable nonpulsatile rotary blood pump, it is necessary to incorporate at least seven features in the system as listed below
and in Table 1. In addition, the pump should be
noiseless, operating independently, and stable. It is also
necessary to eliminate electric and electromagnetic influence inside or outside of the system.

3.1. Smaller size

As for the pulsatile pump, due to the inflow limitation, the maximum pulse rate is in the range of 150
bpm. Therefore, it is necessary to have an effective
stroke volume of over 50 cc, and have a pumping
chamber of 60-65 cc. However, for the rotary blood
pump, the RPM is typically in the range of 2000 for a
centrifugal pump and 10000 for an axial pump. The
rotary blood pump is very small as evidenced by the
axial flow pump (Fig. 1). So the size required for these
pumps that have been developed is in the range of
1110th and 1/50th. Table 2 shows the size of our
pulsatile LVAD [20], centrifugal pump [21] and axial
flow blood pump [22].
3.2. Atraumatic feature
The normalized index of hemolysis (NIH) in most
pulsatile pumps is in the range of 0.04. This is due to
the high dp/dt required to generate a pulsatile flow and
the need for two blood trauma inducing heart valves.
The roller pumps generate an IH level of 0.06. We have
achieved an NIH level of 0.002-0.004 in both centrifugal pumps and in the axial flow blood pump [22,23] by
optimizing the design of pumps and their operational

Y. Nose, K. Kawahito /European

Journal of Cardio-thoracic

Surgery

11 Suppl. (1997) S32-S38

s35

Table 2
Size requirement of ventricular assist device

Height (cm)
Width (cm)
Volume (cc)
Weight (g)

Smallest pulsatile LVAD

(electro-mechanical LVAD)

CIE3 centrifugal pump

DeBakey/NASA
axial flow LVAD

10.1
98.9
310
570

40.0
86.0
130
125

7.0
2.7
15
54

Abbreviations: LVAD; Left ventricular assist device.

parameters (Table 3). The system optimization was

derived not only from an atraumatic feature point of
view, but also from the system efficiency and system
endurance point of view. The higher system efficiency
produces a longer life expectancy in the electrical system. The lower RPM in the system produces the longer
the life of the mechanical system, particularly for the
bearings.
3.3. Anti-thrombogenic feature
In the past, a long-term anti-thrombogenic feature of
a rotary blood pump was considered one of the most
difficult tasks to achieve. However, many groups are
attempting to achieve this objective by a seal-less design, elimination of blood stagnant areas inside the
pump, and a smooth blood-contacting surface. Considering this, a short term centrifugal blood pump called
the ClE3 pump has been developed in our laboratory
[21]. Currently, the process of converting this pump
into a permanent device is underway. This pumps
excellent anti-thrombogenic
feature was achieved by
eliminating an impeller shaft and replacing it with two
pivot bearings incorporated both at the top and bottom
of the pumps impeller. Based on the design of the
pump, effective flow dynamics inside the pump produce
continuous blood washout at both pivot bearing areas,
thus eliminating any thrombogenic areas inside the
pump. Fig. 2 and 3 show the ClE3 pump, there is a
high blood flow at the top bearing area and an effective
secondary flow at the bottom bearing area. All clinically available mechanical heart valves employ the same
basic concept of eliminating any blood stagnant areas.
Since the CIE3 pump eliminates the blood stagnant
regions, particularly at both pivot bearing areas, we are

confident this device will be long term anti-thrombogenie.

3.4. Anti-infection feature
An intrathoracic cardiac prosthesis, such as the
Jarvik-7 TAH, has a tendency to develop device-centered infection [24,25]. This infection occurs after implantation of a man-made prosthesis and material is
very often fatal or requires the removal of the implanted material. Based on this experience, it is proposed that if the intrathoracic cardiac prosthesis is
volumetrically stable and made of a rigid structure, we
can avoid the device-centered infection successfully [26].
The Novacor LVAD and the Therm0 Cardiosystem
LVAD are of this construction.
It is further advantageous if the surface of the device
is texturized because a healthy layer of the tissue capsule will adhere to the surface of the device. This
healthy tissue capsule integrated with the device will
eliminate the possible device-centered infection, not
only inside the chest but also elsewhere in the body [27].
Thus, if the biomaterial is covered with healthy cells,
infection is prevented. In order to avoid device-centered
infection, all the tissue-contacting surfaces are texturized allowing the growth of healthy tissue. We know
the healthy tissue capsule integrated with the device will
eliminate possible device-centered infection [27]. In addition, the device is a volumetrically stable structure
that avoids mechanical damage of the tissue capsules
that forms on the surface [28]. This surface texturized
design is proven to be infection free in longer than
2-year implantations [29]. During the past 10 years, we
intensively investigated the phenomena of tissue capsule
formation on the cardiac prosthesis and its relationship

Table 3
Blood trauma induced by a blood pump

N.I.H.
(g/l00 1)
Abbreviations:

Pulsatile
LVAD

Non-pulsatile
CIE3 centrifugal pump

DeBakey/NASA

0.04 &

< 0.002

<0.003

NIH, normalized index of hemolysis; LVAD, Left ventricular assist device.

axial flow pump

S36

Y. Nose, K. Kawahito /European

Journal of Cardio-thoracic Surgery 1 I Suppl. (1997) S32-S38

Fig. 2. Picture of the ClE3 Gyro pump.

to infection around these devices including compliance

chambers. Even in a volumetrically variable device such
as compliance chamber, the texturized surface structure
proves to avoid device-centered infection [28].
3.5. Durable and simpler design
The life of the currently available centrifugal pump is
limited to a few days due to blood leakage and thrombus formation around the shaft-seal. In order to extend
the pump life, we propose a seal-less centrifugal pump
by replacing the shaft seal with pivot bearings supporting the top and bottom of the impeller in the ClE3
pump (Fig. 3). Due to the durable and simple design of
this pump, the key factor for determining the pump life
is the endurance characteristics of the pivot bearing
system, both at the top and the bottom. That is to say,
life limitation of bearing systems dictates the mechanical
life of the LVAD. Recent endurance studies reveal that
a ceramic-polyethylene
pivot bearing system has an
8-year life as an LVAD [30].
On the other hand, a lower-power-requiring
pump
dictates the electrical life of the LVAD. With excessive
rise in temperature, the motor life will shorten. The
lifetime of the electronic devices and related components
can be calculated using Arrhenius equation:

- >c
Ea

Lf=e

ik

~-- 273
Tj+

I
298 >

where L,- is the lifetime factor, Ea is the activation

energy of the electronic device in electron-volt, k is the
Boltzmans constant, and Ti is the temperature of the
electronic device in centigrade [31]. To calculate the
effect of an increased temperature on the device life, L,is calculated for two temperatures of interest. The ratios
of the two L, s define the ratio of the resulting change
in the device lifetime. Considering the Arrhenius equation, there is a 40% increase in the electronic failure rate
when operating at 42C as opposed to 37C. In the
planned permanent pump system, the motor and pump
casing will be fabricated with titanium, a good heat
transfer is anticipated from the motor to the blood.
Also, some heat can be dissipated into the surrounding
tissue. Since the energy converter and electronics will
use 6 or 7 W under a normal condition, the temperature
rise in the motor will be small with most of its heat
transmitted into the blood and subcutaneous tissue [32].
3.6. Lower energy requirement
Since our ClE3 pump requires only less than 8 W, the
wasted heat is considered to be less than in a pulsatile

Y. Nose, K. Kawahito /European

Fig. 3. The side view of the impeller of the ClE3 Gyro

bearing supporting
the top and bottom of the impeller.

Journal of Cardio-thoracic Surgery I1 Suppl. (1997) .S32-S38

pump.

This pump

pump
which
is typically
in the range of 10 W or higher.
As mentioned, the endurance life of the electronic
components is heavily dependent upon their exposure
to higher temperatures. Since this lower-power-requiring pump generates less wasted heat, we anticipate less
electrical and mechanical failure from the system.
Therefore, the life of the system is expected to be
longer. In addition, we expect less heat dissipation
problems and less thermal damage to the tissue. Thus,
the rotary blood pump is expected to have a longer life
than that of the pulsatile pump.

3.7. Easy controllability

Intrinsic control of a rotary blood pump without any
physiological parameters was once considered to be
difficult. Since a pulsatile pump employs a passive fill
mode, position sensor on the pusher plate will provide
a satisfactory and simple control. On the contrary,
rotary blood pump changes its output due to changes in
afterloads even though the RPM is constantly maintained. It was mistakenly thought that it was necessary
to monitor its operation by an extrinsic parameter, such
as arterial blood pressure or pump output. However, a
recently developed feedback servo utilizing the input
current wave form to regulate the pumps RPM proves
to provide an effective, reliable and automatic control

is a seal-less

centrifugal

pump

by replacing

s37

the shaft seal with pivot

of the rotary blood pump. The pumps intrinsic

parameters, such as voltage and current, demonstrates
sufficient RPM control for the rotary blood pump.

4. Conclusion
Ten years ago, to develop a permanent rotary blood
pump was considered to be an impossible dream. But
now, almost all the technical problems associated in
developing a permanent non-pulsatile rotary blood
pump have been solved. Although achieving this goal is
not an easy task, advance of the technology has made
this idea a reality.

References
[I] Pae WE, Miller CA, Matthews Y, Pierce WS. Ventricular
assist
devices for postcardiotomy
cardiogenic
shock: a combined registry experience. J Thorac Cardiovasc
Surg 1992;104:541-543.
[2] Noon GP. Bio-Medicus ventricular assistance. Ann Thorac Surg
1991;52:180-181.
[3] Curtis JJ, Walls JT, Schmaltz R, Boley TM, Nawarawong
W,
Landreneau
RJ. Experience with the Sarns centrifugal
pump in
postcardiotomy
ventricular
failure. J Thorac Cardiovasc
Surg
1992;104:554-560.
[4] Magovern
GJ, Jr. The biopump and postoperative
circulatory
support. Ann Thorac Surg 1993;55:245-249.

S38

Y. Nose, K. Kawahito / European Journal of Cardio-thoracic Surgery I I Suppl. (1997) S32-S38

[51 Griffith LD, Shoor PM, Dilley RB, Bernstein EF. Beneficial
effects of nonpulsatile left ventricular bypass on myocardial
energy utilization: interaction of oxygen demand and supply.
Trans Am Sot Artif Intern Organs 1978;24:298-304.
Fl Kanamori Y, Shimono T, Tanaka K, Yada I, Kusagawa M.
Effect of left heart assist device for the heart: a comparative
study of asynchronous pulsatile, synchronous pulsatile, and nonpulsatile left heart bypass. Artif Organs 1991;14(suppl):492-496.
[71 Golding LR, Harasaki H, Loop FD, Sukalac R, Reich S, Nose
Y. Use of a centrifugal pump for temporary left ventricular assist
system. Trans Am Sot Artif Intern Organs 1978;24:93-97.
PI Johnston GG, Hammill FS, Johansen KH, Marzec U, Gerard
D, Dilley RB, Bernstein EF. Prolonged pulsatile and nonpulsatile LV bypass with a centrifugal pump. Trans Am Sot Artif
Intern Organs 1976;22:323-331.
[91 Nose Y. My life with the National Institute of Health Artificial
Heart Program. Artif Organs 1990;14:174- 190.
PO1 Golding LR, Jacobs G, Murakami T, Takatani S, Valdes F,
Harasaki H, Nose Y. Chronic nonpulsatile blood flow in an
alive, awake animal 34day survival. Trans Am Sot Artif Intern
Organs 1980;26:251-255.
VII Golding LR, Murakami G, Harasaki H, Takatani S, Jacobs G,
Yada I, Tomita K, Yozu R, Valdes F, Fujimoto LK, Koike S,
Nose Y. Chronic nonpulsatile blood flow. Trans Am Sot Artif
Intern Organs 1982;28:81-85.
WI Yada I, Golding LR, Harasaki H, Jacobs G, Koike S, Yozu R,
Sato N, Fujimoto LK, Snow J, Olsen E, Murabayashi S,
Venkatesen VS, Kiraly R, Nose Y. Physiopathological studies of
nonpulsatile blood flow in chronic models. Tram Am Sot Artif
Intern Organs 1983;24:520-525.
P31 Takatani S, Ozawa K, Golding L, Jacobs G, Murakami T,
Valdes F, Harasaki H, Kiraly R, Nose Y. Comparative evaluation of nonpulsatile and pulsatile cardiac prosthesis. Trans Am
Sot Artif Intern Organs 1980;26:438-443.
1141Valdes F, Takatani S, Jacobs GB, Murakami T, Harasaki H,
Golding LR, Nose Y. Comparison of hemodynamic changes in
a chronic nonpulsatile biventricular bypass (BVB) and total
artificial heart (TAH). Trans Am Sot Artif Intern Organs
1980;26:455-460.
[I51 Nose Y. Nonpulsatile mode of blood flow required for cardiopulmonary bypass and total body perfusion. Artif organs
1993;17:92-102.
[16] Sugita Y, Golding LR, Jacobs G, Harasaki H, Yozu R, Sato N,
Fujimoto LK, Morimoto T, Snow J, Olsen E, Smith W, Murabayashi S, Kambic H, Kiraly R, Nose Y. Comparison of osmotic and body fluid balance in chronic nonpulsatile
biventricular bypass (NPBVB) and total artificial heart (TAH)
experiments. Trans Am Sot Artif Intern Organs 1984;30:148154.
[17] Valdes F, Golding LR, Harasaki H, Takatani S, Jacobs G, Nose
Y. Hemodynamic response to exercise during chronic ventricular
fibrillation and nonpulsatile biventricular bypass (BVB). Trans

Am Sot Artif Intern Organs 1981;27:449-453.

[I81 Yozu R, Golding LAR, Shimomitsu T, Jacobs G, Watanabe T,
Harasaki H, Nose Y. Exercise response in chronic nonpulsatile
and pulsatile TAH animals. Trans Am Sot Artif Intern Organs
1985;31:22-27.
P91 Yozu R, Golding LAR, Jacobs G, Harasaki H, Nose Y. Experimental results and future prospects for a nonpulsatile cardiac
prosthesis. World J Surg 1985;9:116-127.
PO1 Sasaki T, Takatani S, Shiono M, Sakuma I, Glueck J, Noon GP,
Nose Y, DeBakey ME. Development of totally implantable
electromechanical artificial heart systems: Baylor ventricular assist system. Artif Organs 1992;16:407-413.
E-11 Nakazawa T, Makinouchi K, Takami Y, Glueck J, Takatani S,
Nose Y. The effect of the impeller-driver magnetic coupling
distance on hemolysis in a compact centrifugal pump. Artif
Organs 1996;20:252-257.
w-1 Mizuguchi K, Damm G, Benkowsky R, Aber G, Bacak J,
Svjkovsky P, Glueck J, Takatani S, Nose Y, Noon GP, DeBakey
ME. Development of an axial flow ventricular assist device: In
vitro and in vivo evaluation. Artif Organs 1995;19:653-659.
~231Naito K, Mizuguchi K, Nose Y. The need for standardizing the
index of hemolysis. Artif Organs 1994;18:7-10.
~241Kunin CM, Dobbins JJ, Melo JC, Levinson MM, Love K, Joyce
LD, DeVries W. Infectious complications in four long-term
recipients of the Javik-7 artificial heart. JAMA 1988;259:860864.
v51 Griffith BP, Kormos RL, Hardesty RL, Armitage JM, Dummer
JS. The artificial heart: infection-related morbidity and its effect
on transplantation. Ann Thorac Surg 1988;45:409-414.
WI Freed PS, Wasfie T, Bar-Lev A, Hagiwara K, Vemuri D,
Vaughan F, Bernstein L, Gray R, Bernstein I, Kantrowitz A.
Long-term percutaneous access device. Trans Am Sot Artif
Intern Organs 1985;31:230-234.
1271Gristina AG. Biomaterial-centered infection: Microbial adhesion
versus tissue integration. Science 1987;237:1588-1595.
WI Nose Y. Is a totally implantable artificial heart realistic? Artif
Organs 1992;16:19-42.
P91 Sato N, Snow J, Smith W, Kasick J, Kaneko S, Olsen E,
Hillegass D, Harasaki H, Kiraly R, Nose Y. Complacence
chamber - system integration studies. Trans Am Sot Artif
Intern Organs 1984;30:545-549.
[30] Makinouchi K, Nakazawa T, Takami Y, Takatani S, Nose Y.
Evaluation of the wear of the pivot bearing in the Gyro pump
ClE3. Artif Organs 1996;20:523-528.
[31] Stiller W. Arrhenius equation and non-equilibrium kinetics: 100
years Arrhenius equation. Leiptiz: Teubner, 1989.
[32] Tasai K, Takatani S, Orime Y, Damm G, Ohara Y, Naito K,
Makinouchi K, Mizuguchi K, Matsuda Y, Shimono T, Glueck J,
Noon GP, Nose Y. Successful thermal management of a totally
implantable ventricular assist system. Artif Organs 1994;18:4953.